Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
This application claims benefit of 63/454507, filed March 24, 2023. Claims 1-27 are pending in this application and examined on the merits herein.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-6 and 20-26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Draget et al. (US pre-grant publication 2014/0163108, cited in PTO-892)
Independent claim 1 is directed to an oil-in-water emulsion which comprises aqueous and lipid phases, and a first chemotherapeutic agent in the lipophilic phase. Independent claim 25 claims a method of treating a tumor in a subject comprising administering such a composition. Independent claim 20 claims a water-in-oil emulsion wherein a lipophilic drug is dispersed within the aqueous phase.
Draget et al. discloses a composition wherein a drug is dispersed within an emulsion, in a solid particulate form, for example a hydrophilic drug in the lipid phase of an oil-in-water emulsion or a lipophilic drug in the water phase of a water-in-oil emulsion. (p. 1 paragraph 6) In one embodiment the therapeutic agent is an anticancer agent. (p. 3 paragraph 34) Additionally, Draget et al. discloses a method for treating conditions including cancer comprising administering this composition to a subject in need thereof. (p. 4 paragraph 36) For these reasons Draget et al. anticipates claims 1, 20, and 25.
Regarding claims 2 and 21, Draget et al. discloses an embodiment wherein the solid drug particles are in crystalline form. (p. 2 paragraph 15) Regarding claims 3-5, 22-24, and 26, Draget et al. further discloses various arrangements of both hydrophilic and lipophilic drugs dissolved and/or dispersed in both the aqueous and lipophilic phases of the composition, including embodiments of all of these claims. Furthermore regarding the relative dissolution and elution rates of the two drugs, the fact that these are two different drugs in two different phases of the composition would indicate that they would be expected to have different release profiles, with one eluting and dissolving faster than the other. Regarding claim 6, Draget et al. discloses an embodiment wherein the oil phase comprises a triglyceride. (p. 4 paragraph 40)
For these reasons Draget et al. anticipates the present claims.
Claims 1, 3, 6, 15, 16, 18, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Modi. (US pre-grant publication 2015/0231069, cited in PTO-892)
Independent claim 1 is directed to an oil-in-water emulsion which comprises aqueous and lipid phases, and a first chemotherapeutic agent in the lipophilic phase. Modi discloses a drug delivery system wherein an active chemotherapeutic drug is entrapped in a nano-sized carrier. (p. 1 paragraph 9) This drug delivery system can be used for chemotherapeutic drugs such as paclitaxel. (p. 2 paragraph 10) The beads are further blended with an edible oil to form an emulsion. (p. 2 paragraph 11) These compositions are reasonably considered to be drug-containing emulsions according to claims 1 and 3. Regarding claims 6 and 16, the oil used in the emulsion is preferably both long and medium chain triglycerides, including soybean oil, (p. 5 paragraph 56) and stearic acids. (p. 6 paragraph 60) Regarding claim 18, table 1 on p. 7 of Modi discloses stability of the emulsion for 12 months. Regarding claims 15 and 19, p. 2 paragraph 30 of Modi discloses that the therapeutic agent can include doxorubicin or docetaxel.
For these reasons Modi anticipates the present claims.
Claims 1, 3, 6, 8-10, 13-16, 18, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen. (US pre-grant publication 2007/0207173, cited in PTO-892)
Independent claim 1 is directed to an oil-in-water emulsion which comprises aqueous and lipid phases, and a first chemotherapeutic agent in the lipophilic phase. Claim 3 further requires that the chemotherapeutic agent be dissolved in the lipophilic phase. Chen discloses an oil-in-water emulsion in which a substantially water insoluble pharmaceutically active agent is dissolved in the oil phase along with vitamin E succinate. (p. 1 paragraphs 14-15) In a particular embodiment the water insoluble drug is docetaxel, thereby anticipating present claims 1, 3, and 19. Regarding claim 6, in some embodiments the oil is vegetable oil such as soybean oil. (p. 9 paragraph 86) Regarding claim 8, in one embodiment the composition comprises a phospholipid in a concentration of 1% or 2%. (p. 11 paragraph 139) Regarding claim 9, in one embodiment the oil phase is present in an amount of about 10, 12, 15, 17, or 20% by weight. (p. 9 paragraph 91) Regarding claim 13, p. 9 paragraph 92 of Chen discloses for example a 5:1 or 4:1 ratio of vegetable oil to MCT, which would result in the claimed ratio. Regarding claim 14, p. 9 paragraph 81 of Chen describes ratios of pharmacological agent to vegetable oil ranging from 1:100 to 1:5, which would all fall within the range recited in this claim. Regarding claim 15, in one embodiment the therapeutic agent is doxorubicin, an anthracycline. (p. 6 paragraph 68) Regarding claim 16, p. 10 paragraph 97 of Chen describes the phospholipid as potentially containing a stearate fatty acid. Regarding claim 18, example 5 on pp. 15-17 of Chen discloses emulsions that are stable for as long as 12 months.
For these reasons Chen anticipates the present claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Draget et al. (US pre-grant publication 2014/0163108, cited in PTO-892)
The disclosure of Draget et al. is discussed above. While Draget et al. does not specifically disclose the particular ratio of oil to aqueous phase recited in precent claim 9, p. 4 paragraph 51 of Draget discloses a preferred ratio of 1:19-3:1, or 5-75%, which overlaps the claimed range of 10-40%. It would have been obvious to one of ordinary skill in the art at the time of the invention to determine the appropriate ratio of these two phases, so as to arrive at the specific claimed ratio.
Therefore the invention taken as a whole is prima facie obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Modi as applied to claims 1, 3, 6, 15, 16, 18, and 19 above, and further in view of Taylor et al. (US pre-grant publication 2019/0175495, cited in PTO-1449)
The disclosure of Modi is discussed above. Modi further discloses that the composition comprises an inert polymer matrix such as sodium hyaluronate at a composition of 5-40%, (p. 5 paragraph 54) and further includes glycerin as a surfactant or emulsifier. (p. 6 paragraphs 57-58) Modi does not specifically disclose a formulation comprising tyramine substituted hyaluronic acid and glycerol at the specifically recited concentration.
Taylor et al. discloses a hydrogel based bonding matrix for encapsulating drug reservoirs. (p. 1 paragraphs 6-7) This hydrogel allows for better control of the rate of drug elution. (p. 1 paragraphs 8-9) In a particular embodiment the drug reservoirs are suspended in a binding matrix such as tyramine-substituted hyaluronic acid. (p. 3 paragraph 25) While the primary embodiment described is injection, Taylor et al. also discloses oral administration of the composition. (p. 7 paragraph 92, p. 11 paragraph 143)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use tyramine-substituted HA as the inert polymer matrix in the dosage forms described by Modi. One of ordinary skill in the art would have seen this to be obvious because Taylor et al. discloses using tyramine-substitute HA for a similar purpose, and discloses the advantage of better control of drug release rate.
It would additionally have been obvious to one of ordinary skill in the art at the time of the invention to determine an appropriate concentration of glycerin to use as a surfactant in the compositions as described by Modi. One of ordinary skill in the art would have considered it to be obvious to determine the optimal concentration of surfactant to include in such a composition.
Therefore the invention taken as a whole is prima facie obvious.
Claims 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Chen. (US pre-grant publication 2007/0207173, cited in PTO-892)
The disclosure of Chen is discussed above. Chen et al. further discloses the composition comprising dextrose or sorbitol as an osmotic agent (p. 11 paragraph 141) or bulking agent. (p. 11 paragraph 147) While Chen does not specifically disclose the concentration of dextrose or sorbitol recited in present claims 11 and 12, it would have been obvious to one of ordinary skill in the art at the time of the invention to include these compounds in the recited concentrations. One of ordinary skill in the art would have found it to be obvious to determine the appropriate concentration of each excipient such as an osmotic or bulking agent to include in the composition. Furthermore, while p. 11 paragraph 148 suggests a bulking agent concentration of 5-30% of the composition, a large number of bulking agents are recited and it is indicated that concentrations of multiple agents can be used. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to prepare a composition including multiple bulking agents, each at a lower percentage than that which would be used as a single agent.
Therefore the invention taken as a whole is prima facie obvious.
Conclusion
Claims 1-16 and 18-26 are rejected. Claims 17 and 27 are objected to for depending from a rejected base claims but would be allowable if rewritten in independent form incorporating all the limitations of the rejected base claims and any intervening claims.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 7/20/2026
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